Unfortunately, investing time, resources and energy into potential therapies, only to see them fail at late-stage clinical trials, is still an all too common occurrence. Inefficiencies in traditional and commonly employed preclinical models are partly to blame for these failures and the ensuing costs that are carried on to payers and end users alike. Thankfully the next generation of 3D Cellular Models is making progress towards predictive safety and efficacy screens that are more relatable to the clinic, though there is still lots to be done in terms of improving their reliability, scalability and reproducibility. Join us for Cambridge Healthtech Institute’s Third Annual 3D Cellular Models conference, where this promising preclinical model will be explored and evaluated, where future steps towards more accurate and reliable preclinical trials will be taken.

Final Agenda

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Recommended All Access Package:

27 November: Organ-on-a-Chip and MicroPhysiological Systems

27 November Dinner Course: SC3: The Origins, Optimization and Application of Organ-on-a-Chip Systems

28-29 November: Optimizing Leads and Predicting Drug Toxicity

29-30 November: 3D Cellular Models

29 November Dinner Course: SC5: Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy

Thursday 29 November

12:30 Registration

IPSC BASED 3D MODELS I

13:25 Welcome Remarks

Joel Hornby, BSc, Conference Director, Cambridge Healthtech Institute

13:30 Chairperson’s Opening Remarks

Hansjoerg Keller, PhD, Senior Investigator I, Musculoskeletal, Novartis Institutes for BioMedical Research

13:35 Human Heart-in-a-Jar from iPSC for Disease Modelling and Drug Screening

Ronald A. Li, PhD, Director and Professor, Ming Wai Lau Center for Reparative Medicine, Karolinska Institutet

Traditional drug development is an inefficient and expensive process with unacceptably high failure rates. Major species-specific differences limit the ability of animal models to predict human cardiotoxicity, the dominant reason for attrition. Here, I will present various human ESC/iPSC-derived engineered heart constructs that our group has designed specifically for studying electrophysiology and contractility, including our latest fluid-ejecting “human heart-in-a-jar” that uniquely enables the measurements of clinically complex parameters such as cardiac output, ejection fraction, PV loops.

14:05 An in vitro 3D Kidney Model – Generation and Application in a Pharmaceutical Setting

Anna Jonebring, MSc, Senior Scientist, Translational Genomics, Discovery Sciences IMED Biotech Unit, AstraZeneca

A disease like chronic kidney disease (CKD), affecting approximately 10% of the population, is one of the areas where there is a great unmet need for innovative pharmacological therapies. Within AstraZeneca we are working with human iPSCs derived 3D kidney models in a platform approach to drive the TI/TV activities as well as developing a highly efficient model for safety/toxicology applications. Combining the 3D model with CRISPR/Cas9, Next-Generation Sequencing (NGS), functional testing and advanced imaging techniques, our 3D kidney platform is evolving and becoming an essential part in our drug discovery process.

14:35 A Novel High-Throughput Multi-Parametric Drug Screening Method for 3D Tumor Spheroids Using Celigo Image Cytometer

Suzanne Riches, PhD, Technology Research & Development, Manager, Nexcelom Bioscience LLC

There is an increase in utilizing 3D spheroid for drug screening. We demonstrated a cancer drug scoring method using multi-parametric analysis to rank the anti-cancer effects of drugs on tumor spheroids. The assays conducted were growth inhibition, perimeter cell-death, and viability. Drugs can be screened to identify potential drug candidates.

15:05 Interactive Breakout Discussion Groups - View Details

This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking.

Microphysiological Systems for Drug Screening"

Moderator: Hansjoerg Keller, PhD, Sr. Investigator I, Musculoskeletal, Novartis Institutes for BioMedical Research

• Key advantages over classical 2D cell culture models
• Reliability and translatability of human systems
• Applicability, throughput and cost effectiveness

16:05 Refreshment Break in the Exhibit Hall with Poster Viewing

ADVANCED MODELS FOR DRUG DISCOVERY

16:45 Novel 3D Hepatic in vitro Systems for Studies of Chronic Drug Toxicity and Liver Disease

Magnus Ingelman-Sundberg, PhD, BSc.Med, Professor, Department of Physiology and Pharmacology, Karolinska Institutet

Using a model of 3D PHH spheroids we observed that drug metabolism was preserved for several weeks of cultivation and that transcriptomic, proteomic and metabolomics analyses revealed similar phenotype as in freshly isolated hepatocytes. In addition, using these 3D spheroid systems we have been able to mimic different liver disease like NAFLD, NASH and fibrosis and found the system suitable for evaluation of mechanisms behind and for identification of drug candidates. In the lecture recent results describing the properties and usefulness of the system will be presented.

17:15 Drug Screening Using Biofabricated 3D Tissue-in-a-Dish Models
Marc Ferrer, PhD, Team Lead, NIH Chemical Genomics Center, NIH/NCATS
As the success rate from entry into clinical testing to drug approval remains low, 3D tissue models are being developed as alternative in vitro functional assays for drug development. However, the biofabrication of architecturally and physiologically defined human 3D tissue models in a microplate format for drug testing remains a challenge. We will discuss how NCATS is using biofabrication techniques to create a catalog of 3D tissues models for screening.

17:45 Contracting Muscle Models in a Dish for Physiological Drug Screening

Hansjoerg Keller, PhD, Senior Investigator I, Musculoskeletal, Novartis Institutes for BioMedical Research

There is a high need for in vitro human microphysiological assay systems in order to enhance the translatability of preclinical drug discovery and development efforts. Using a 3D bioprinting approach, we have developed a new screening platform for the automated fabrication of functional human skeletal muscle tissue models attached between two posts in microwells, which can be electrically stimulated. It is a promising new in vitro exercise model to identify drugs regulating muscle force and fatigue.

18:15 Close of Day and Dinner Short Course Registration

19:00 – 21:30 Recommended Dinner Short Course*

SC5: Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy

* Separate registration required.

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Friday 30 November

8:30 Registration and Morning Coffee

IPSC BASED 3D MODELS II

8:55 Chairperson’s Remarks

Marine Kraus, PhD, Specialist, Group Leader, Stem Cell, Nestle Institute of Health Sciences SA

9:00 Organoids: A Next-Generation in vitro Model That Captures Clinical Response

Lyle Armstrong, PhD, Professor of Cellular Reprogramming & CSO, Newcells Biotech Ltd., Institute of Genetic Medicine, Newcastle University

Toxicity testing based upon animal models or transformed cell lines is not always an accurate representation of the response of human tissues and organs to xenobiotic substances. The development of human pluripotent stem cells, which are capable of generating many of the cell types found in the adult body, may be an effective solution to address this problem therefore this lecture will attempt to present not only the background of what pluripotent stem cells are and how they are made but also how we can use them to produce versatile new toxicity assays for use in pharmaceutical development.

9:30 In vitro Generation of Functionally Mature Beta-Cells from Adult Human iPSCs

Marine Kraus, PhD, Specialist, Group Leader, Stem Cell, Nestle Institute of Health Sciences SA

Islet transplantation has demonstrated that replacement of the beta-cell mass in diabetic patients is able to restore endogenous glycaemic control. Stem-cell therapies hold great promise for generating a replenishable supply of insulin producing beta-cells for transplantation. In the present studies, we report the in vitro generation of functionally mature beta-cells from human iPSCs. These newly generated beta-cells display mature features and exhibit glucose regulated insulin secretion, displaying the first and second insulin release phases characteristic of human islets.

10:00 Coffee Break in the Exhibit Hall. Last chance for poster viewing.

STEM CELL BASED 3D MODELS

10:45 Engineered Fail-Safe and Allo-Tolerated 3D Tissue for in situ Drug Manufacturing and Delivery to Treat Disease

Andras Nagy, PhD, Senior Investigator, Lunenfeld-Tanenbaum Research Institute, Sinai Health System

Pluripotent Stem cells have accelerated the development of new avenues for targeting diseases with cell therapies. Numerous of these are currently on their way. We addressed two significant hurdles of cell therapies; safety and long-term allograft tolerance without immune suppression. The combination of these two allows the generation of stable allogeneic 3D tissues which could be a source of secreted biologics to treat diseases, for example, endocrine and metabolic deficiencies.

Nuria Montserrat, PhD, Group Leader, Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC)

Our aim is to facilitate basic knowledge on kidney engineering providing novel approaches facilitating renal maturation and function. We have generated kidney organoids from human pluripotent stem cells. In parallel, we have developed biomimetic inks for bioprinting 3D kidney structures. Lastly, using a novel transplantation method we have further maturated and vascularized kidney organoids. We provide innovative solutions when translating these technologies into the clinical setting.

11:45 Organoids: A Next-Generation in vitro Model That Captures Clinical Response

Robert Vries, PhD, Managing Director, Stichting Hubrecht Organoid Technologies

The laboratory of Hans Clevers, the founder of HUB, previously discovered the identity of adult stem cells in many human tissues such as intestine and liver (Barker et al., Nature 2007; Huch et al., Nature 2013). More recently, we were able to demonstrate that the in vitro response of organoids directly correlates with the clinical outcome of the patient from which the organoid was derived (Dekkers et al., Sci Trans Med 2016; Sachs et al., Cell 2018). In addition, we have now developed a novel system that allows the co-culture of organoids with immune cells to study the effect of immune modulating drugs.

12:15 Enjoy Lunch on Your Own

COMPLEX CELL SYSTEMS

13:40 Chairperson’s Remarks

Glyn N. Stacey, PhD, CEO, International Stem Cell Banking Initiative

13:45 Quality Control and Standardisation for Complex Cell Systems

Glyn N. Stacey, PhD, CEO, International Stem Cell Banking Initiative

The use of cell cultures requires attention to identity of starting cells, awareness of potential contamination and attention to accurate documentation of reagents, cell sources and protocols (Coecke et el., 2005). A further development of this best practice guidance will be described is being led by the Centre for Alternatives to Animal Testing and incorporates pluripotent stem cell culture, 3D cultures and tissue on a chip systems (Pamies et al., 2016).

14:15 3D Spheroids: Bridging the Gap Between In Vitro and In Vivo

Sakshi Garg, PhD, Head of laboratory, Discovery Pharmacology, Merck KGaA

Over the last decades, data has emerged highlighting that conventional 2D cell culture tumor models fail to capture important aspects of tumor physiology. The predictive value of phenotypic screening is directly correlated to how closely the chosen assay represents the in vivo conditions. To mimic the cell physiology and biological characteristics of tumors we use 3D cellular spheroids combined with a co-culture system to recapture the tumor microenvironment better.

14:45 The Phenion Full Thickness Skin Model: A Versatile Tool for Efficacy and Toxicological Testing of Dermally Applied Compounds

Dirk Petersohn, PhD, Director, Beauty Care Technologies - Biological & Clinical Research, Henkel AG & Co. KGaA

Skin is often the site of first contact for many substances. The Phenion® Full Thickness skin models mimic native human skin in its histology and a wide spectrum of biochemical properties. Primary human keratinocytes form a fully differentiated epidermis that connects through the basement membrane with the underlying collagenous dermis that is populated with fibroblasts of the same donor. Its biological equivalence with human skin makes the tissue model perfectly suited for efficacy testing of substances or toxicological assessments, as exemplified with the 3D-Skin Comet assay.

15:15 aProximate™ in vitro Renal Proximal Tubule Cell Model and Clinically Relevant Biomarkers as a Predictive Screening Platform to Understand Nephrotoxicity

Colin Brown, PhD, Associate Professor at Institute of Cell & Molecular Biosciences, Medical School, Newcells Biotechnology, Newcastle University

We have developed a series of in vitro primary renal proximal tubule models as a platform to understand the proximal tubule handling of drug molecules and to screen drug molecules for nephrotoxic potential using clinically relevant biomarkers of renal damage. We have now characterised a new 3D-multilayer model of the proximal tubule including proximal tubule cells, interstitial fibroblasts and endothelial cells which may improve differentiation and longevity in culture further.

15:45 Close of Conference

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